Novel approaches to treatment of acute myeloid leukemia (AML) in CALGB protocols focus on reversing chemoresistance. Targeted resistance mechanisms include multidrug resistance (MDR) mediated by cell membrane proteins that function as drug efflux pumps (in CALGB 9420, CALGB 9621, CALGB 9720 and the current CALGB 19808), as well as, in the next grant period, resistance to apoptosis mediated by overexpression of the anti-apoptotic protein Bcl-2 (in CALGB 10201). In testing the efficacy of therapies directed at biologic targets, it is critical to test for presence of the biologic target in the primary tumor cell and to assure that the biologic endpoints are achieved. In addition, it is important to identify competing mechanisms of chemoresistance that may be a source of treatment failure. Correlative laboratory studies measuring therapeutic targets of AML treatment protocols are the central focus of the new Target Validation Project within the CALGB Leukemia Correlative Sciences grant. The therapeutic targets to be studied in the next grant period, determined by current and upcoming treatment protocols, are P-glycoprotein (Pgp) and Bcl-2 overexpression.